Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Cell Cycle. 2011 Feb 15;10(4):584-91. doi: 10.4161/cc.10.4.14728.
At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.
在着床时,小鼠胚胎由三个组织组成:上胚层、滋养外胚层和原始内胚层。随着发育的进行,上胚层继续形成胎儿,而滋养外胚层和原始内胚层则产生具有重要胚胎模式和营养作用的胚胎外结构。早期胚胎发育过程中基因表达发生剧烈变化,这需要在不同水平上进行调控。miRNA 是过去十年中新兴的小非编码 RNA,作为基因表达的重要转录后抑制剂。miRNA 在哺乳动物早期发育中的作用才刚刚开始被阐明。为了深入了解 miRNA 在早期小鼠胚胎不同谱系中的功能,我们深入分析了 miRNA 成熟蛋白 Dicer 突变的胚胎和胚胎外干细胞的表型。这项研究表明,miRNA 参与调节早期胚胎中的细胞信号和内稳态。具体而言,我们确定了 miRNA 在调节胚胎外内胚层中的 Erk 信号通路、胚胎外组织中的细胞周期进程以及上胚层中的细胞凋亡中的作用。